生物等效性
药品
化学
体外
抗氧化剂
药理学
抗坏血酸
生物利用度
药代动力学
体内
色谱法
生物化学
医学
食品科学
生物技术
生物
作者
Dongmei Lu,Bhagwant Rege,Andre Raw,Jingyue Yang,Khondoker Alam,Chris Bode,Liang Zhao,Patrick J. Faustino,Fang Wu,Diaá M. Shakleya,Elisa A. Nickum,Bing V. Li,Rong Wang,Ethan Stier,Blair Miezeiewski,Rachana Patel,Ashley Boam,Robert Lionberger,David A. Keire,Lawrence X. Yu
标识
DOI:10.1016/j.xphs.2024.05.033
摘要
Reformulation with addition of antioxidants is one potential mitigation strategy to prevent or reduce nitrosamine drug substance-related impurities (NDSRIs) in drug products. To explore whether there could be other approaches to demonstrate bioequivalence for a reformulated oral product, which typically needs in vivo bioequivalence studies to support the changes after approval, the effects of antioxidant on the in vitro permeability of BCS III model drug substances were investigated to see whether there could be any potential impact on drug absorption. Six antioxidants were screened and four (ascorbic acid, cysteine, α-tocopherol and propyl gallate) were selected based on their nitrosamine inhibition efficiencies. The study demonstrated that these four antioxidants, at the tested amounts, did not have observable impact on the in vitro permeability of the BCS III model drug substances across Caco-2 cell monolayers in the In Vitro Dissolution Absorption System (IDAS). An in vitro permeability study could be considered as part of one potential bioequivalence bridging approach for reformulated low-risk immediate release solid oral products and oral suspension products. Other factors such as the influence of antioxidants on intestinal transporter activities should be considered where appropriate.
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